Faculty Bibliography

BACKGROUND:Walkable neighborhoods are purported to impact a range of cardiometabolic outcomes through increased walking, but there is limited research that examines multiple cardiometabolic outcomes. Additionally, few Walk Score (a novel measure of neighborhood walkability) studies have been conducted in a European context. We evaluated associations between neighborhood Walk Score and selected cardiometabolic outcomes, including obesity, hypertension and heart rate, among adults in the Paris metropolitan area. METHODS AND RESULTS/RESULTS:We used data from the second wave of the RECORD Study on 5993 participants recruited in 2011-2014, aged 34-84 years, and residing in Paris (France). To this existing dataset, we added Walk Score values for participants' residential address. We used multilevel linear models for the continuous outcomes and modified Poisson models were used for our categorical outcomes to estimate associations between the neighborhood Walk Score (both as a continuous and categorical variable) (0-100 score) and body mass index (BMI) (weight/height2 in kg/m2), obesity (kg/m2), waist circumference (cm), systolic blood pressure (SBP) (mmHg), diastolic blood pressure (DBP) (mmHg), hypertension (mmHg), resting heart rate (RHR) (beats per minute), and neighborhood recreational walking (minutes per week). Most participants lived in Walker's Paradise (48.3%). In multivariate models (adjusted for individual variables, neighborhood variables, and risk factors for cardiometabolic outcomes), we found that neighborhood Walk Score was associated with decreased BMI (β: -0.010, 95% CI: -0.019 to -0.002 per unit increase), decreased waist circumference (β: -0.031, 95% CI: -0.054 to -0.008), increased neighborhood recreational walking (β: +0.73, 95% CI: +0.37 to +1.10), decreased SBP (β: -0.030, 95% CI: -0.063 to -0.0004), decreased DBP (β: -0.028, 95% CI: -0.047 to -0.008), and decreased resting heart rate (β: -0.026 95% CI: -0.046 to -0.005). CONCLUSIONS:In this large population-based study, we found that, even in a European context, living in a highly walkable neighborhood was associated with improved cardiometabolic health. Designing walkable neighborhoods may be a viable strategy in reducing cardiovascular disease prevalence at the population level.

Strong evidence now supports the notion that organophosphate pesticides damage the fetal brain and produce cognitive and behavioral dysfunction through multiple mechanisms, including thyroid disruption. A regulatory ban was proposed, but actions to end the use of one such pesticide, chlorpyrifos, in agriculture were recently stopped by the Environmental Protection Agency under false scientific pretenses. This manuscript describes the costs and consequences of this policy failure and notes how this case study is emblematic of a broader dismissal of scientific evidence and attacks on scientific norms. Scientists have a responsibility to rebut and decry these serious challenges to human health and scientific integrity.

BACKGROUND: Research of adults and school-aged children suggest a neurodevelopmental basis for psychiatric disorders. We examined whether infant neuromotor development predicted internalizing and externalizing problems in young children. METHODS: In Generation R, a population-based cohort in the Netherlands (2002-2006), trained research assistants evaluated the neuromotor development of 4006 infants aged 2 to 5 months by using an adapted version of Touwen's Neurodevelopmental Examination (tone, responses, and senses and other observations). We defined nonoptimal neuromotor development as scores in the highest tertile. Mothers and fathers rated their children's behavior at ages 1.5, 3, 6, and 10 years with the Child Behavior Checklist (n = 3474, response: 86.7%). The associations were tested with generalized linear mixed models. RESULTS: Overall, neuromotor development predicted internalizing scores, but no association was observed with externalizing scores. Nonoptimal muscle tone was associated with higher internalizing scores (mothers' report: beta = .07; 95% confidence interval [CI]: 0.01 to 0.13; fathers' report: beta = .09, 95% CI: 0.00 to 0.16). In particular, nonoptimal low muscle tone was associated with higher internalizing scores (mothers' report: beta = .11; 95% CI: 0.05 to 0.18; fathers' report: beta = .13; 95% CI: 0.04 to 0.22). We also observed an association between senses and other observations with internalizing scores. There was no relationship between high muscle tone or reflexes and internalizing scores. CONCLUSIONS: Common emotional problems in childhood have a neurodevelopmental basis in infancy. Neuromotor assessment in infancy may help identify vulnerability to early internalizing symptoms and offer the opportunity for targeted interventions.

BACKGROUND: Early-life exposure to bisphenol A (BPA) has been implicated to play a role in the development of obesity. OBJECTIVE: A systematic review with meta-analyses of experimental rodent studies was conducted to answer the following question: does early-life exposure to BPA affect the obesity-related outcomes body weight, fat (pad) weight, and circulating and tissue levels of triglycerides, free fatty acids (FFA), and leptin? METHODS: The methodology was prespecified in a rigorous protocol using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) approach. Using PubMed and EMBASE, we identified 61 articles that met the inclusion criteria. The risk of bias and the methodological quality of these articles were assessed using the SYRCLE Risk of Bias tool, and a confidence-rating methodology was used to score the quality of evidence. Meta-analyses were performed using random effect models and standardized mean differences (SMDs), or, where possible, mean differences (MDs) were calculated. RESULTS: Overall summary estimates indicated significant positive associations between BPA and fat weight [SMD=0.67 (95% CI: 0.53, 0.81)], triglycerides [SMD=0.97 (95% CI: 0.53, 1.40)], and FFA [SMD=0.86 (95% CI: 0.50, 1.22)], and a nonsignificant positive association with leptin levels [MD=0.37 (95% CI: -0.14, 0.87)] and a significant negative association with body weight were estimated [MD=-0.22 (95% CI: -0.37, -0.06)]. Subgroup analyses revealed stronger positive associations for most outcome measures in males and at doses below the current U.S. reference dose of 50mug/kg/d compared with doses above the reference dose. It should be noted that there was substantial heterogeneity across studies for all outcomes assessed and that there was insufficient information to assess risk of bias for most studies. CONCLUSIONS: Findings from our systematic review suggest that early-life exposure to BPA may increase adiposity and circulating lipid levels in rodents. https://doi.org/10.1289/EHP1233.

BACKGROUND: Food contact articles (FCAs) are manufactured from food contact materials (FCMs) that include plastics, paper, metal, glass, and printing inks. Chemicals can migrate from FCAs into food during storage, processing, and transportation. Food contact materials' safety is evaluated using chemical risk assessment (RA). Several challenges to the RA of FCAs exist. OBJECTIVES: We review regulatory requirements for RA of FCMs in the United States and Europe, identify gaps in RA, and highlight opportunities for improving the protection of public health. We intend to initiate a discussion in the wider scientific community to enhance the safety of food contact articles. DISCUSSION: Based on our evaluation of the evidence, we conclude that current regulations are insufficient for addressing chemical exposures from FCAs. RA currently focuses on monomers and additives used in the manufacture of products, but it does not cover all substances formed in the production processes. Several factors hamper effective RA for many FCMs, including a lack of information on chemical identity, inadequate assessment of hazardous properties, and missing exposure data. Companies make decisions about the safety of some food contact chemicals (FCCs) without review by public authorities. Some chemical migration limits cannot be enforced because analytical standards are unavailable. CONCLUSION: We think that exposures to hazardous substances migrating from FCAs require more attention. We recommend a) limiting the number and types of chemicals authorized for manufacture and b) developing novel approaches for assessing the safety of chemicals in FCAs, including unidentified chemicals that form during or after production. https://doi.org/10.1289/EHP644.

BACKGROUND: Large amounts of various chemical contaminants, including perfluoroalkyl substances (PFASs), were released at the time of the World Trade Center (WTC) disaster. Thousands of children who lived and/or attended school near the disaster site were exposed to these substances but few studies have examined the possible consequences related to these exposures. OBJECTIVES: To examine the relationship of PFASs serum levels with cardiometabolic profile in children and adolescents enrolled in the World Trade Center Health Registry (WTCHR) and a matched comparison group. METHODS: We evaluated WTCHR enrollees who resided in New York City and were born between September 11, 1993 and September 10, 2001, and a matched comparison group consisting of individuals who were ineligible for WTCHR participation upon distance of their home, school or work from the WTC and lack of participation in rescue and recovery activities. Matching was based on date of birth, sex, race, ethnicity, and income. We assessed exposure to PFASs, as measured by serum levels and association with cardiometabolic profile as measured by arterial wall stiffness, body mass index, insulin resistance, fasting total cholesterol, HDL, LDL and triglycerides. RESULTS: A total of 402 participants completed the study and serum samples were analyzed from 308 participants, 123 in the WTCHR group and 185 in the comparison group. In multivariable regression analysis, after adjusting for relevant confounders, we observed a significant, positive association of perfluorooctanoic acid (PFOA) with triglycerides (beta coefficient=0.14, 95% CI: 0.02, 0.27, 15.1% change), total cholesterol (beta coefficient=0.09, 95% CI: 0.04, 0.14, 9.2% change), and LDL cholesterol (beta coefficient=0.11, 95% CI: 0.03, 0.19, 11.5% change). Perfluorohexanesulfonic acid levels were associated with decreased insulin resistance (beta coefficient=-0.09, 95% CI: -0.18, -0.003, -8.6% change); PFOA and perfluorononanoic acid were associated with increased brachial artery distensibility. CONCLUSIONS: This research adds to our knowledge of the physical health impacts in a large group of children exposed to the WTC disaster. Abnormal lipid levels in young adults might be an early marker of atherosclerosis and cardiovascular diseases and our findings highlight the importance of conducting longitudinal studies in this population.

BACKGROUND: Socioeconomic analysis is currently used in the Europe Union as part of the regulatory process in Regulation Registration, Evaluation and Authorisation of Chemicals (REACH), with the aim of assessing and managing risks from dangerous chemicals. The political impact of the socio-economic analysis is potentially high in the authorisation and restriction procedures, however, current socio-economic analysis dossiers submitted under REACH are very heterogeneous in terms of methodology used and quality. Furthermore, the economic literature is not very helpful for regulatory purposes, as most published calculations of health costs associated with chemical exposures use epidemiological studies as input data, but such studies are rarely available for most substances. The quasi-totality of the data used in the REACH dossiers comes from toxicological studies. METHODS: This paper assesses the use of the integrated probabilistic risk assessment, based on toxicological data, for the calculation of health costs associated with endocrine disrupting effects of triclosan. The results are compared with those obtained using the population attributable fraction, based on epidemiological data. RESULTS: The results based on the integrated probabilistic risk assessment indicated that 4894 men could have reproductive deficits based on the decreased vas deferens weights observed in rats, 0 cases of changed T3 levels, and 0 cases of girls with early pubertal development. The results obtained with the Population Attributable Fraction method showed 7,199,228 cases of obesity per year, 281,923 girls per year with early pubertal development and 88,957 to 303,759 cases per year with increased total T3 hormone levels. The economic costs associated with increased BMI due to TCS exposure could be calculated. Direct health costs were estimated at euro5.8 billion per year. CONCLUSIONS: The two methods give very different results for the same effects. The choice of a toxicological-based or an epidemiological-based method in the socio-economic analysis will therefore significantly impact the estimated health costs and consequently the political risk management decision. Additional work should be done for understanding the reasons of these significant differences.

Context: Common environmental contaminants can disrupt normal thyroid function, which plays essential but varying roles at different ages. Objective: To evaluate the relationship of perchlorate, thiocyanate, and nitrate, three sodium-iodide symporter (NIS) inhibitors, and thyroid function in different age-sex-stratified populations. Design, Setting, Participants, and Intervention: This was a cross-sectional analysis of data from the 2009-2012 National Health and Nutrition Examination Surveys (NHANES) evaluating the exposure to perchlorate, thiocyanate, and nitrate in 3,151 participants aged 12-80. Main Outcome Measure: Blood serum free thyroxine (FT4) as both a continuous and categorical variable. We also assessed blood serum thyroid stimulating hormone (TSH). Results: Controlling for serum cotinine, BMI, total daily energy consumption, race/ethnicity, and poverty-to-income ratio, for each log unit increase in perchlorate, FT4 decreased by 0.03 ng/dL in both the general population (p=0.004) and in all women (p=0.005), and by 0.06 ng/dL in adolescent girls (p=0.029), corresponding to 4% and 8% decreases relative to median FT4, respectively. For each log unit increase thiocyanate, FT4 decreased by 0.07 ng/dL in adolescent boys (p=0.003), corresponding to a 9% decrease relative to median FT4, respectively. Conclusions: Our results indicate that adolescent boys and girls represent vulnerable subpopulations to the thyroid-blocking effects of NIS symporter inhibitors. These results suggest a valuable screening and intervention opportunity.

BACKGROUND: Previous studies identified associations between maternal obesity and childhood neurodevelopment, but few examined paternal obesity despite potentially distinct genetic/epigenetic effects related to developmental programming. METHODS: Upstate KIDS (2008-2010) recruited mothers from New York State (excluding New York City) at approximately 4 months postpartum. Parents completed the Ages and Stages Questionnaire (ASQ) when their children were 4, 8, 12, 18, 24, 30, and 36 months of age corrected for gestation. The ASQ is validated to screen for delays in 5 developmental domains (ie, fine motor, gross motor, communication, personal-social functioning, and problem-solving ability). Analyses included 3759 singletons and 1062 nonrelated twins with >/=1 ASQs returned. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated by using generalized linear mixed models accounting for maternal covariates (ie, age, race, education, insurance, marital status, parity, and pregnancy smoking). RESULTS: Compared with normal/underweight mothers (BMI <25), children of obese mothers (26% with BMI >/=30) had increased odds of failing the fine motor domain (aOR 1.67; confidence interval 1.12-2.47). The association remained after additional adjustment for paternal BMI (1.67; 1.11-2.52). Paternal obesity (29%) was associated with increased risk of failing the personal-social domain (1.75; 1.13-2.71), albeit attenuated after adjustment for maternal obesity (aOR 1.71; 1.08-2.70). Children whose parents both had BMI >/=35 were likely to additionally fail the problem-solving domain (2.93; 1.09-7.85). CONCLUSIONS: Findings suggest that maternal and paternal obesity are each associated with specific delays in early childhood development, emphasizing the importance of family information when screening child development.